Tetrahydrocannabinol derivatives

Hardman, H.F., Domino, E.F., and Seevers, M.H. General pharmacological actions of some synthetic tetrahydrocannabinol derivatives. Pharmacol. Rev. 23 295-315, 1971. 

Mechoulam, R., Lander, N Brener, A., and Zahalka, J. (1990) Synthesis of the individual, pharmacologically distinct enantiomers of a tetrahydrocannabinol derivative. Tetrahedron Asymmetry 1, 315-318. 

Duffley RP, Handrick GR, Uliss DB, Lambert G, Dalzell HC, Razdan RK (1980) Synthesis of 2 - and 3 -Acetoxyolivetols [5-(2- and 3-Acetoxypentyl)-1,3-benzene Diols] Key Intermediates in the Synthesis of Tetrahydrocannabinol Derivatives. Synthesis 733... 

Carroll AR, Bowden BE, Coll JC. A new tetrahydrocannabinol derivative from the ascidian Synoicum castella-tum.Aus. J. Chem. 1993 46(7) 1079-1083. 

Tetrahydrocannabinol (= THC)-11-carboxylic acid 290 Tetrahydrocortiso 221 Tetrahydrocortisone 221 Tetrahydrosteroids 222 Tetrazolium salts, reduction 61 Thalidomide 45 -, hydrolysis products 45 Thiabendazole 307, 308 Thiamine 235, 236, 397 Thickening agents 179 Thin-layer chromatography, advantage 5 -, numbers of publications per year 6 Thiobarbiturates 45,66 Thiocarbamide derivatives 322 Thiocarbamides, N -ary I-N -benzenesulfo-nyl- 248,249 Thiochrome 395... 

In the first chapter, Flemming et al. review the chemistry, biosynthesis, metabolism and biological activities of tetrahydrocannabinol and its derivatives. 

Classical cannabinoids (CCs) are tricyclic terpenoid derivatives bearing a benzopyran moiety. This class includes the natural product (-)-delta-nine-tetrahydrocannabinol (Fig. 8, 1) and the other pharmacologically active constituents of the plant Cannabis sativa. 

Several products are derived from the cannabis plant (table 10.1). Hashish and charas are the dried resin exuded from the female flowers. These have the highest content of A9-tetrahydrocannabinol (TFIC) at 10-20% and have the most potent psychoactive effects. Ganja and sinsemilla are the dried tops of the female plants, which averages 5-8%. Marijuana and bhang are derived from the rest of the plant and have the lowest TFIC concentration (2-5%). 

The advances in isolation methods made possible a clarification of the chemistry of cannabis. In 1963, our group reisolated CBD and reported its correct structure and stereochemistry. A year later we finally succeeded in isolating pure A -tetrahydrocannabinol (A -THC), elucidated its structure, obtained a crystalline derivative and achieved a partial synthesis from CBD. Several years later, a minor psychotomimetically active constituent, A -THC, was isolated from marijuana. Whether this THC isomer is a natural compound, or an artifact formed during the drying of the plant, remains an open problem. 

A -3,4-cis-THC has now been found in Cannabis sativa (Phenotype III) other papers reporting the characterization of compounds from Cannabis sativa concern conclusive identification and synthesis of cannabinodiol, " which is known to result from the photochemical irradiation of cannabinol (Vol. 7, p. 51), and the identification of A -tetrahydrocannabinolic acid " and (+)-cannabitriol (263) " (263) and the corresponding C-2 ethyl ether may be epoxide-derived. " ... 

Cannabinoids are the psychoactive components of marijuana, which has the species name Cannabis sativa. Concentrations of cannabinoids vary greatly from plant to plant. The original strains of this plant species contain very little of these psychoactive components and have been used for many centuries for their great fiber qualities. Strains of Cannabis that may be smoked for psychoactive effects on average contain about 4 percent cannabinoid derivatives. The most active of these derivatives is the compound A9-tetrahydrocannabinol (THC), shown in Figure 14.33 on page 504. 

Cannabis resin, obtained from the flowering tops of hemp plants, contains a number of dibenzopyrans. The main active constituent is (-)-A1-3,4-numbering system is used). Cannabinol derivatives have slight pharmaceutical potential, e.g. as antiemetics and analgesics, but because of their hallucinatory effects and habituation tendency, which have led to their widespread abuse, they are not prescribed. 

Irradiation of several members of the cannabinoid family has provided useful routes to some derivatives. Cannabichromene (576) is converted into cannabicyclol (577) when it is irradiated in r-butyl alcohol-acetone <71JCS(C)796) and tetrahydrocannabinolic acid (578) is aromatized to cannabinolic acid (579) (70CPB1327). 

Resorcinols. Condensation of this diene with the ketal of a fi- keto acid derivative results in a resorcinol with complete regiocontrol. Thus, the TiCl4-catalyzed reaction of 1 with ketal ester 2 results in the resorcinol 3 in 72% yield. However, use of the acid chloride 4 corresponding to 2 in the same reaction results in the isomeric resorcinol, methyl olivetolate (5). The regiocontrol is based on the reactiv ity order acid chloride > ketal > ester. The resorcinol 5 was used in a biomimetic synthesis of the chromene A1 -tetrahydrocannabinol (6), a component of marijuana. 

FIGURE 18.2 Chemical structures of A9-tetrahydrocannabinol (A9-THC) derived from marijuana, and the endogenous cannabimimetic eicosanoid, anadamide (arachidonylethanolamide), identified in the human brain. 

The active principle of Salvia divinorum, salvinorin A, is derived from the leaves of the plant. Chemically, salvinorin A is a neoclerodane diterpene, one of a group of nitrogen-containing terpene compounds that have psychotropic properties. Two other such compounds are tetrahydrocannabinol and absinthe. Purified salvinorin A can be obtained from an ether extract of the leaves, which is then concentrated by chromatography and repeated crystallization. 

The plasma of a dog intravenously administered solutions of l c-A -tetrahydrocannabinol was monitored with time after heptane extraction by both radiochemical analysis and electron-capture GLC of the derivative of the appropriately collected eluate fraction from normal phase HPLC. Typical plots of the time course of the results from both methods are given in Figure 7. 

Tetrahydrocannabinol, the major psychoactive compound in marijuana, is derived in the Cannabis plant from olivetol and geranyl pyrophosphate. Details of the pathway are unknown. Make some suggestions and outline a labelling experiment to establish whether your suggestions are correct. 

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